title: Novel therapeutic strategy for uterine endometrial cancers.
abstract: In general, tumors induce angiogenic factors specific to them, which leads to angiogenesis with tumor progression. However, angiogenesis in uterine endometrial cancers is complicated because the hormone dependency in their growth also modifies the angiogenic potential. Therefore, angiogenic potential in uterine endometrial cancers must be thoroughly analyzed. The upstream of the vascular endothelial growth factor (VEGF) gene conserves estrogen-responsive elements. Progesterone primed with estrogen induces thymidine phosphorylase (TP) in the uterine endometrium. Sex steroid-dependent VEGF and TP are highly expressed in early-stage and well-differentiated uterine endometrial cancers, and basic fibroblast growth factor (bFGF) is highly expressed in advanced and poorly differentiated uterine endometrial cancers. A transcriptional factor for angiogenesis, E26 transformation specific (ETS-1), is linked to VEGF in well-differentiated uterine endometrial cancers, and to bFGF in poorly differentiated uterine endometrial cancers. Therefore, even if dedifferentiation and angiogenic switching occur due to tumor progression and long-term hormone therapy, the inhibition of ETS-1, along with inhibition of the main angiogenic factors, may be an effective strategy to suppress uterine endometrial cancers as a novel antiangiogenic therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. jf@gifu-u.ac.jp
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujimoto
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism / Q000627:therapeutic use; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic; D050784:Proto-Oncogene Protein c-ets-1 / Q000627:therapeutic use*
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D050784:Proto-Oncogene Protein c-ets-1